Field of the Invention
The invention generally relates to a vaccine and diagnostic for Lyme disease. In particular, the invention provides a Lyme disease vaccine and diagnostic that includes linear Borrelia outer surface protein A (OspA) epitopes and/or Borrelia outer surface protein C (OspC) epitopes, usually from multiple distinct phyletic groups.
Background of the Invention
Lyme disease is the most common arthropod-borne disease in North America and Europe, where in some areas up to 3% of the population is infected annually. Lyme disease is caused by the spirochetes Borrelia burgdorferi, B. garinii and B. afzelii. Transmission to mammals occurs through the bite of infected Ixodes ticks. Infection results in a multi-systemic inflammatory disease with early stage symptoms that may include erythema migrans, low-grade fever, arthralgia, myalgia, and headache. Late stage clinical manifestations can be severe and may include in part, arthritis and neurological complications. In addition, Lyme disease has significant socio-economic costs, manifested by reductions in outdoor recreational and social activities due to concerns about tick exposure.
The antigen used in first generation Lyme disease vaccines (e.g. LYMErix) was Outer surface protein A (OspA). OspA is only expressed by spirochetes in ticks, thus anti-OspA bactericidal activity occurs in the vector. However, a major drawback to the use of full-length OspA was the potential (whether real or perceived) for adverse events secondary to vaccination, such as the development of arthritis caused by immunological cross-reactivity with human proteins (e.g. LFA-1). This was a major factor in the withdrawal from the market of the original OspA-based LYMErix vaccine.
U.S. Pat. No. 6,248,562 (Jun. 19, 2001) to Dunn and Luft describes chimeric Borrelia proteins that can be used as immunodiagnostic reagents and vaccine immunogens against Borrelia infection.
U.S. Pat. Nos. 6,872,550 and 6,486,130 (Mar. 29, 2005, and Nov. 26, 2002, respectively) both to Livey, describe constructs for use a vaccines against Lyme disease.
U.S. Pat. No. 7,008,625 (Mar. 7, 2006) to Dattwyler et al. discloses chimeric Borrelia proteins that can be used as immunodiagnostic reagents and vaccine immunogens against Borrelia infection
The publication “Recombinant Chimeric Borrelia Proteins for Diagnosis of Lyme Disease” (Maria J. C. Gomes-Solecki et al. 2000. J. Clin. Microbiol., 38: 2530-2535) also describes recombinant chimeric proteins.
Despite the above-referenced technologies, to date the prior art has failed to provide an efficacious vaccine for use in the prevention and/or treatment of Lyme disease.